A radiolabeled antibody targeting CD123+ leukemia stem cells - initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML

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Abstract

Radioimmunotherapy (RIT) with anti-CD123 monoclonal antibody CSL360 modified with nuclear translocation sequence (NLS) peptides and labeled with the Auger electron-emitter, 111In (111In-NLS-CSL360) was studied in the prevalent NOD/SCID mouse AML engraftment assay. Significant decreases in CD123+ leukemic cells and impairment of leukemic stem cell self-renewal were achieved with high doses of RIT. However, NOD/SCID mice were very radiosensitive to these doses. At low non-toxic treatment doses, 111In-NLS-CSL360 demonstrated a trend towards improved survival associated with decreased spleen/body weight ratio, an indicator of leukemia burden, and almost complete eradication of leukemia from the bone marrow in some mice.

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Leyton, J. V., Gao, C., Williams, B., Keating, A., Minden, M., & Reilly, R. M. (2015). A radiolabeled antibody targeting CD123+ leukemia stem cells - initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML. Leukemia Research Reports, 4(2), 55–59. https://doi.org/10.1016/j.lrr.2015.07.003

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